Throughout this application, various publications are referenced by Arabic numerals within parentheses. Full citations for these publications may be found at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
Transforming growth factor .beta. (TGF-.beta.) is part of a family of multifunctional proteins which appear to modulate, alone or in combination with other molecules, cell proliferation and differentiation. Reportedly, TGF-.beta., which comprises a mature a precursor and a pro region of the precursor form, contains a subclass of molecules designated TGF-.beta.1, -.beta.2, -.beta.3, -.beta.4, and-.beta.5 (24, 25, 26).
Mature TGF-.beta. has been isolated from various species. Murine, bovine, human, and porcine TGF-.beta. have been isolated and show very little difference in amino acid composition (26, 27, 28, 29).
The CDNA sequence of mature TGF-.beta., its expression in both normal and transformed cells, and methods of producing biologically active mature TGF-.beta. in eucaryotic cells have been described (26, 28, 29, 54, 55).
Antibodies directed to mature TGF-.beta.1 and -.beta.2 have previously been described (32, 33, 34, 35, 36). Because of the high homology between the various isoforms of mature TGF-.beta., these antibodies exhibit substantial cross reactivity. Antibodies which are specifically directed to human mature TGF-.beta.3 and exhibit no substantial cross reactivity with other TGF-.beta.3 isoforms have not been described.